The influence of type and quantity of model drug on the extrusion/spheronization of mixtures with microcrystalline cellulose. I. Extrusion parameters.

摘要

Five model drugs, (methyl, propyl and butyl paraben, 4-hydroxybenzoic acid and propyl gallate), similar in their chemical structure were mixed with microcrystalline cellulose and water in different proportions and forced through a ram extruder. The overall water movement was measured by the difference between the initial water in the formulation and the water content in the plug remaining after extrusion was completed. The differences in theoretical and practical volume occupancy of the materials inside the barrel were calculated to look for trapped air inside the barrel. The steady-state extrusion force for each formulation was recorded. All five materials demonstrated differences in behaviour during extrusion. The relationship between each of the three properties measured and both the drug-load and initial water content was examined, to establish the potential relationship that existed between the differences due to the drug models. The five drug models were divided into two sub-groups, when examining the way that they underwent extrusion. Methyl, propyl and butyl paraben formed one group while 4-hydroxybenzoic acid and propyl gallate formed the other group. Within the former group the relationship between steady-state extrusion force and the percentage of drug and water present tended to be lower than those in the latter group. For the former group these relationships were non-linear.